Chlamydia trachomatis is the most common sexually transmitted bacterial pathogen in the U.S. with an estimated 5 million cases annually. Studies have been in progress to define the clinical spectrum of chlamydial infection, to develop rapid diagnostic assays and to examine the pathogenesis of chlamydial infection in experimental animal models. In screening over 2000 men and women attending STD clinics, chlamydia genital infections continue to be common with infection rates of 10%-15%. Chlamydia infections tend to have the characteristics of a prevalent infection since infection rates vary little by either sex, reason for clinic attendance, number of sex partners or the patient's relationship with their sexual partners. The predominate serovars present in this population are serovar D (34.7%) and serovar F (47.8%), with serovar F more likely to induce or maintain an inflammatory response in urethritis (p = 0.027). A relatively high prevalence of anti-chlamydia antibodies was noted in 65% of the men and 94% of the women, and higher titers of chlamydia pacific antibodies (-< 1:128) were more common among women (39%) than in men (15%). Patients with recurrent gonorrhea were significantly more likely to experience recurrence of chlamydia due to the same serovar, suggesting that microbiologically inapparent or persistent chlamydial infections may be reactivated during recurrent gonococcal infection. Diagnostic assays including antigen detection by phase EIA and polymerase chain reaction (PCR) have been developed. By incorporating soluble hybridization with an RNA probe and a fluorometric EIA to detect RNA-DNA hybrids, we have been able to quantitate the amount of DNA amplified by PCR. In an experimental animal model where viability of C. trachomatis can be monitored, we have demonstrated persistence of chlamydial DNA by PCR in monkeys who have become culture negative. This persistence of chlamydial DNA may possibly contribute to either a sustained hypersensitivity response or a latent state which is inhibited by the presence of neutralizing antibody and cell mediated immunity. Further studies are planned to examine the persistence of chlamydia in patients to further define the immunopathogenesis of chlamydia and its capability for inducing latent infection. Additional studies are also planned to examine the prevalence and clinical presentation of C .pneumoniae (TWAR) infection as an etiologic cause of pneumonia in pediatric, adult and geriatric populations.